Progestogens versus oestrogens and progestogens for irregular uterine bleeding associated with anovulation

Hickey, M, Higham, J, Fraser, I S, Hickey, Martha, Higham, Jenny M, Fraser, Ian

Dysfunctional uterine bleeding (DUB) is excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognisable pelvic or systemic disease. Anovulation may be inferred from a number of observations but, in the normal clinical situation, anovulation is often assumed when a woman presents with heavy, prolonged or frequent bleeding, particularly in those who are at the extremes of reproductive life and in women known to have polycystic ovarian syndrome. Menstrual bleeding that is irregular or excessive is poorly tolerated by the majority of women. Changes in the length of the menstrual cycle generally imply disturbances of the hypothalamo-pituitary-ovarian (HPO) axis. In anovulatory DUB with acyclic (irregular) oestrogen production there will be no progesterone withdrawal from oestrogen primed endometrium and so cycles are irregular. Prolonged oestrogen stimulation may cause a build up of endometrium with erratic bleeding as it breaks down and is expelled. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle, in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination are already widely used in the management of irregular or excessive bleeding due to DUB but the regime, dose and type of progestogen used varies widely, with little consensus about the optimum treatment approach. To determine the effectiveness and acceptability of progestogens alone and oestrogens and progestogens in combination in the management of irregular bleeding associated with anovulation. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched 4 May 2007), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to May 2007), EMBASE (1985 to May 2007), CINAHL (1982 to May 2007), Biological Abstracts (1969 to May 2007), Current Contents (1980 to 2007) and reference lists of articles. All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular bleeding associated with anovulation. Study quality assessment and data extraction were carried out independently by two review authors. Both authors were experts in the content matter. No randomised trials were identified which compared progestogens with oestrogens and progestogens or with placebo in the management of irregular bleeding associated with anovulation. Only one small, non-randomised study compared two progestogen regimes in the management of heavy and irregular bleeding in women with confirmed anovulation. One randomised study compared the effects of two progestogens on endometrial histology in women with a variety of menstrual symptoms, half of whom had cystic glandular hyperplasia. There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular bleeding associated with anovulation. Further research is needed to establish the role of these treatments in the management of this common gynaecological problem.